A Randomized, Double-blind, Placebo-controlled Multicenter Study of Secukinumab (AIN457) to Examine the Clinical Efficacy and the NSAID-sparing Effect of Secukinumab Over 16 Weeks in Patients With Ankylosing Spondylitis (ASTRUM)
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 211
- 试验地点
- 1
- 主要终点
- Proportion of Patients Who Achieved ASAS20 Response in the Pooled Secukinumab Group Compared With the Placebo Group at Week 12
研究概览
简要总结
This study assessed the clinical Assessment of SpondyloArthritis international Society (ASAS) 20 response to secukinumab and evaluated to which extent concomitant nonsteroidal anti-inflammatory drug (NSAID) treatment can be reduced in patients treated with secukinumab or placebo following an initial run-in phase of stable NSAID therapy.
详细描述
This was a phase IV, 20-week, randomized, double-blind, 3-arm, placebo-controlled, parallel-group, multicenter study to examine the clinical response of secukinumab treatment in patients with ankylosing spondylitis as measured by the Assessment of SpondyloArthritis international Society (ASAS) 20 response and the nonsteroidal anti-inflammatory drug (NSAID)-sparing effect. This study evaluated to which extent nonsteroidal anti-inflammatory drug (NSAID) treatment can be reduced between Week 4 and Week 12 in patients randomized to secukinumab 150 mg or placebo following an initial run-in phase of 4 weeks on stable NSAID therapy. Two NSAID tapering approaches were evaluated in this study:
- an early tapering approach in which NSAID were tapered at the start of secukinumab treatment,
- a delayed tapering approach in which NSAID were tapered following 4 weeks of secukinumab treatment.
Patients were randomized 1:1:1 to one of the following treatment groups:
- Secukinumab - delayed NSAID tapering: Induction with secukinumab 150 mg s.c. once per week (Week 0, 1, 2, 3 and 4) followed by maintenance with secukinumab 150 mg s.c. every 4 weeks (Week 8, 12, 16 and 20), with intermittent placebo injections at Week 5, 6, 7, 17, 18 and 19 to maintain the blind. NSAID tapering allowed from Week 4 (delayed tapering).
- Secukinumab - early NSAID tapering: Placebo at weeks 0, 1, 2, 3 to maintain the blind; followed by induction with secukinumab 150 mg s.c. once per week (Week 4, 5, 6, 7, 8) and maintenance with secukinumab 150 mg s.c. every 4 weeks (Week 12, 16 and 20), with intermittent placebo injections at Week 17, 18 and 19 to maintain the blind. NSAID tapering allowed from Week 4 (early tapering).
- Placebo: Placebo s.c. at Week 0, 1, 2, 3, 4, 5, 6, 7, 8 and 12. After the Week 16 assessments of the secondary endpoint had been performed, these patients received weekly doses of secukinumab 150 mg s.c. (Week 16, 17, 18, 19 and 20). NSAID tapering allowed from Week 4.
The primary objective of the study was to demonstrate that the efficacy of secukinumab 150 mg subcutaneous (s.c.) injection (with NSAID tapering) is superior to placebo based on the proportion of patients achieving an ASAS20 response at Week 12. To show superiority, both secukinumab treatment arms were pooled and compared against placebo.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of active AS with prior documented radiologic evidence fulfilling the Modified New York criteria for AS
- •Active AS assessed by total BASDAI ≥ 4 (0-10) at baseline
- •Spinal pain as measured by BASDAI Question 2 ≥ 4 cm on a 0-10 cm numeric rating scale at baseline
- •Total back pain as measured by VAS ≥ 40 mm (0-100 mm) at baseline
- •Patients should have been on at least 2 different NSAIDs at the highest recommended dose for at least 4 weeks prior to randomization, with an inadequate response or failure to respond, or less if therapy had to be reduced due to intolerance, toxicity or contraindications
- •Patients must report regular intake of NSAIDs of at least 50% of the highest recommended dose at Screening.
- •Patients with prior TNFα inhibitor therapy must report regular intake of NSAIDs of at least 50% of the highest recommended dose at baseline after the appropriate washout
- •Patients are required to be on a stable dose of NSAIDs for at least 2 weeks before randomization
- •Patients who have previously been on a TNFα inhibitor will be allowed entry into study after an appropriate wash-out period prior to randomization
- •Patients who have been on a TNFα inhibitor (not more than two) must have experienced an inadequate response to previous or current treatment given at an approved dose for at least 3 months prior to randomization or have been intolerant to at least one administration of an anti-TNFα agent.
- •Patients taking MTX or sulfasalazine are allowed to continue their medication and must have taken it for at least 3 months and be on a stable dose for at least 4 weeks prior to randomization
排除标准
- •Chest X-ray or MRI with evidence of ongoing infectious or malignant process.
- •Previous exposure to Secukinumab or any other biologic drug directly targeting IL-17 or IL-17 receptor
- •Patients previously treated with any biological immunomodulating agents, except those targeting TNFα
- •Patients who have taken more than two anti-TNFα agents
- •Pregnant or nursing (lactating) women.
- •History of ongoing, chronic or recurrent infectious disease or evidence of tuberculosis infection.
- •Patients who are intolerant to NSAIDs
研究组 & 干预措施
Secukinumab - delayed NSAID tapering
Induction with secukinumab 150 mg s.c. once per week (Week 0, 1, 2, 3 and 4) followed by maintenance with secukinumab 150 mg s.c. every 4 weeks (Week 8, 12, 16 and 20), with intermittent placebo injections at Week 5, 6, 7, 17, 18 and 19 to maintain the blind.
NSAID tapering allowed from Week 4 (delayed tapering).
干预措施: Secukinumab (AIN457) 150 mg s.c. (Drug)
Secukinumab - early NSAID tapering
Placebo at weeks 0, 1, 2, 3 to maintain the blind; followed by induction with secukinumab 150 mg s.c. once per week (Week 4, 5, 6, 7, 8) and maintenance with secukinumab 150 mg s.c. every 4 weeks (Week 12, 16 and 20), with intermittent placebo injections at Week 17, 18 and 19 to maintain the blind.
NSAID tapering allowed from Week 4 (early tapering).
干预措施: Secukinumab (AIN457) 150 mg s.c. (Drug)
Placebo
Placebo s.c. at Week 0, 1, 2, 3, 4, 5, 6, 7, 8 and 12. After the Week 16 assessments of the secondary endpoint had been performed, these patients received weekly doses of secukinumab 150 mg s.c. (Week 16, 17, 18, 19 and 20).
NSAID tapering allowed from Week 4.
干预措施: Placebo - Secukinumab (AIN457) 150 mg s.c. (Drug)
结局指标
主要结局
Proportion of Patients Who Achieved ASAS20 Response in the Pooled Secukinumab Group Compared With the Placebo Group at Week 12
时间窗: Baseline, Week 12
ASAS (Assessment of SpondyloArthritis International Society criteria) 20 response is defined as an improvement from baseline of ≥20% and ≥1 unit on a scale of 0-10 in at least three of the four ASAS main domains and no worsening of ≥20% and ≥1 unit on a scale of 0-10 in the remaining domain. The four main ASAS domains are: Patient's global assessment of disease activity, back pain, function represented by ability to perform specific tasks (from Bath Ankylosing Spondylitis Disease Activity Index \[BASDAI\]) and inflammation represented by mean duration and severity of morning stiffness. Non-responder imputation was applied for missing data.
次要结局
- Proportion of Patients Who Achieved ASAS20 Response in Each Secukinumab Group (Delayed NSAID Tapering and Early NSAID Tapering) Compared With the Placebo Group(Baseline, Week 12, Week 16)
- Mean Change From Baseline in ASAS-NSAID Score at Week 12(Baseline, Week 12)
- Mean Change From Baseline in ASAS-NSAID Score in Each Secukinumab Group After 12 Weeks of Exposure (at Week 12 in the Secukinumab-delayed NSAID Tapering Group and at Week 16 in the Secukinumab-early NSAID Tapering Group)(Baseline, Week 12 (delayed NSAID tapering), Week 16 (early NSAID tapering))
- Mean Change From Baseline in the BASDAI Total Score(Baseline, Week 12, Week 16)
- Mean Change From Baseline in Health-related Quality of Life as Measured by the Short Form-36 Health Survey (SF-36) Physical Component Summary (PCS) Score(Baseline, Week 12)